Loren Frank, PhD

How is your brain able to generate thoughts and images of places other than your immediate surroundings? For example, you are sitting at your desk after a long day at work. You want to get home as fast as possible. You think to yourself, “Should I take the highway or back streets?” The highway could be jammed with traffic, but the back roads have so many stoplights. You aren’t actively driving. Yet, your brain simulates and evaluates which route is best, drawing upon information (images and experiences) stored as memories. Amazing. These sorts of thoughts are essential for survival – and this is true for animals ranging from mice to humans.   

Dr. Loren Frank, PhD and his laboratory are exploring how the brain uses past experience to generate new ideas as a foundation for planning, forecasting, and decision making. Read on for more information about this fascinating area of research!   

Many animals do not simply reflexively react to their local environment, but instead use memories of past experiences to plan and guide behavior. The brain can effectively run “simulations” of what could happen in the future, based on what has happened in the past—this  is a type of imagination. But how does a scientist define and quantify imagination? Dr. Loren Frank defines imagination at the simplest level as “patterns of brain activity that don’t correspond to reality but nevertheless have some interpretive meaning.”  

The Frank lab studies imagination in a brain region called the hippocampus. This is a brain region that stores memories of everyday life and allows these memories to be retrieved. But the hippocampus does not simply replay memories like a video screen, representing and replaying our surrounding world. Rather, individual nerve cells are grouped together into new functional ensembles based upon past experience. Remarkably, if the hippocampus is removed in a human, the patient can have trouble imagining a scene.  

One particularly important type of ensemble in hippocampus is referred to as ‘place cells’. Once established, place cells are active when an animal occupies a particular location in space. To record the activity of these ‘place cells’, the Frank lab places tiny arrays of micro-electrodes into the rodent hippocampus and records as an animal moves around within an environment. Imagine a rat with a baseball hat perched on its head, running around it’s home cage, doing normal, everyday rat things. The baseball hat houses microelectrodes and signal amplifiers that relay the miniscule electrical impulses that are generated by each of thousands of nearby neurons to computers that constantly record those events. The electrodes are novel flexible polymers embedded with minute electronics that can be inserted into the brain. The flexibility helps ensure that the electrode does not damage the brain as the animal moves. As it turns out, when recorded for sufficiently long periods of time (about 10 minutes), place cell activity is highly predictive of an animal’s position in the surrounding environment.  

But, there is a wrinkle – one that is very important for understanding how the Frank lab studies imagination. Occasionally, they observe that place cells do something new, appearing to forecast a possible future location while an animal is moving through space. This can happen when an animal is faced with a choice point, a fork in the road. It is as if the place cells are reporting out the process of decision making. This is evidence of imagination! Obviously, this is non-trivial to figure out when acquiring and analyzing petabytes of information recorded from the rat brain. Frank’s lab has developed complex decoding models to make sense of the neural signals that they observe.   

Recent advances by the Frank lab are thought provoking. When an animal reaches a fork in the road, it can cycle between the two options as fast as eight times per second! And, as the animal approaches the choice point, it already begins to ramp up the imaginative, decision-making process. In summary, when Frank discusses memory and imagination, he emphasizes a connection between past and future. He states, “Memories are not just about the past - they are about the future…they allow you to take the past experience and imagine possible futures by recreating simulations in your brain and then evaluating the simulations to try to figure out what to do next”.   

Ultimately, Frank’s goal is to understand how humans can run through the “what if’s” that might exist in the future, playing out future scenarios in their heads. There are many fascinating things to consider moving forward. For example, if the brain can transcend reality (meaning to think about something that has not yet occurred), what prevents it from generating delusional thoughts? And, indeed, we are all aware that the brain does become delusional in neurological and psychiatric disorders such as schizophrenia, major depression, and neurodegeneration. These disorders may relate to the encoding of imagination and our ability to make informed predictions about the future. Once again, this highlights the importance of connecting past and future within neuronal ensembles to rationally predict, plan, and make decisions about our future.  

For as long as Frank could remember the goal had been to be a scientist. At an early age he thought it would be the moons and stars (astrophysics). When he hit high school, the goal became physics and quantum mechanics. Later, in college, he decided that physics problems were too large. He could solve physics equations but felt he was unlikely to make fundamental contributions in the way that many great theoretical physicists had in the past. He made an unlikely pivot to Cognitive Psychology.   

An experience as a summer intern spawned his love for the hippocampus. At that moment, he realized that one could study cognition and memory by analyzing the signals that are transmitted by individual neurons - this was what he wanted to do! That summer experience led to graduate school and beyond. He describes his training period as some of the hardest times of his life. But he cites mentors that were transformative during this time, including Matt Wilson PhD, a professor at MIT and Emory Brown, M.D., Ph.D., a professor at MIT and Harvard. Eventually Frank was invited to an interview at UCSF for a faculty position. He described this visit as the single most transformative scientific experience of his life. He never knew a place could be so friendly, encouraging, smart and interactive. There was no looking back. He has been at UCSF since June 2003.